We are engaged in determining the relation between the cessation of cellular proliferation, terminal differentiation, and senescence with particular emphasis on the metabolism and behavior of small nuclear RNA's (snRNA's). We are using as test systems Friend's mouse leukemia cells (FLC's) as models of cells that senesce very rapidly after the in vitro induction of differentiation, rat myoblasts as models of cells that senesce quite slowly after the induction of terminal differentiation, and human diploid fibroblasts which appear to senesce independently of any differentiation process. With all 3 systems, cell proliferation ceases before any signs of senescence are evident. We have begun the basic characterization of snRNA synthesis and metabolic stability under various growth conditions (including those conditions that do not allow cell replication, regardless of the differentiation state, or the "normal" programmed cessation of proliferation) for FLC's before and after the induction of differentiation to hemoglobin-producing cells and for human fibroblasts (WI-38) at various stages of programmed aging that occurs in vitro. Although characteristic patterns of snRNA synthesis and behavior associated with different physiological conditions are emerging, it is still to early to give precise definition and quantification to those patterns.